Cannabidiol Treatment Is Ineffective for Arthritic Pain

The medicinal potential of the Cannabis sativa plant — commonly referred to as marijuana — and the more than 100 active chemicals that it produces (collectively known as cannabinoids) have been the subject of intense scientific and political controversy for decades.[1],[2] Cannabidiol is one chemical found in cannabis. Unlike tetrahydrocannabinol (THC) — the main mind-altering chemical in marijuana — cannabidiol by itself does not have rewarding properties that produce a “high.”[3]

The Food and Drug Administration has approved only one purified form of cannabidiol, the prescription oral solution EPIDIOLEX, just to treat seizures associated with three rare and severe forms of childhood-onset epilepsy (Lennox-Gastaut syndrome, Dravet syndrome and tuberous sclerosis).[4]

Despite the suggestion that cannabinoids, including cannabidiol, may have pain-relieving or anti-inflammatory effects, the totality of the evidence thus far has led international experts to conclude that these chemicals should not be recommended for pain management.[5],[6] Results of a randomized clinical trial from Denmark published online in the journal Pain in August 2021 reinforces that conclusion by showing that cannabidiol is ineffective as a treatment for arthritis pain.

Background on arthritis

Arthritis, which literally means joint inflammation, is a blanket term for over 100 different illnesses that affect joints and tissues around joints.[7] Depending on the type of arthritis, symptoms may include joint pain, tenderness, redness, swelling and stiffness; impaired mobility; fever; weight loss; breathing problems; and rashes or itches, among others.[8]

Among the most common forms of arthritis are osteoarthritis (tissue breakdown in the joints of the hands, knees, hips, neck or lower back typically related to aging or prior injury), rheumatoid arthritis (an autoimmune disease that mainly attacks the joints) and psoriatic arthritis (related to psoriasis, an autoimmune disease that also causes red and white scaly patches on the skin).

Recent estimates indicate that 59 million U.S. adults have some form of arthritis, and over one-third of these adults limit their usual activities because of such disease.[9] Osteoarthritis is the most common form of arthritis, affecting an estimated 33 million U.S. adults.[10] Rheumatoid arthritis and psoriatic arthritis are far less common than osteoarthritis, affecting approximately 5 of every 1,000 adults and 1 to 2 of every 1,000 people, respectively.[11],[12]

One goal of treatment for arthritis is to minimize the pain and discomfort that accompanies these diseases. Accordingly, first-line treatment for such ailments are nonpharmacologic approaches such as weight loss (to take the pressure off of inflamed joints), exercises (including physical and occupational therapies), the use of joint braces or other assistive devices like canes and, if needed, topical or oral nonsteroidal anti-inflammatory drugs (NSAIDs).[13],[14] Rheumatoid and psoriatic arthritis often additionally require treatment with immunosuppressing disease-modifying antirheumatic drugs (DMARDs).

The cannabidiol trial[15]

At a single Danish university hospital center, 136 adult patients with either hand osteoarthritis or psoriatic arthritis experiencing at least moderate pain despite other treatment were randomized to receive oral cannabidiol (70 subjects) or a placebo (66 subjects) for 12 weeks. Trial enrollment occurred between November 2018 and September 2020. The initial daily oral dose of cannabidiol was 10 milligrams (mg) once daily for two weeks, then 10 mg two to three times daily. Subjects were urged to continue their usual analgesic medications used prior to enrollment.

The primary outcome was patient-reported pain based on an established scale from 0 to 100, with 100 corresponding to pain that was the worst imaginable, during the previous 24 hours at the end of the 12-week study period. To enter the trial, reported pain had the be at least 30 on this 100-point scale.

Other outcomes assessed were sleep quality, depression, anxiety and pain catastrophizing scores, also based on patient reporting. “Pain catastrophizing” occurs when an individual ruminates, magnifies or despairs regarding pain they may experience or anticipate.[16] These additional outcomes were included because chronic pain patients often experience poor sleep quality, depression and anxiety.

The mean age of the subjects was 62 years, with 65% being female and 57% having hand osteoarthritis. The mean pain score at the beginning of the trial across all subjects was 52 for the cannabidiol group and 61 for the placebo group.

After 12 weeks of treatment, the cannabidiol- and placebo-group subjects reported nearly identical pain-level reductions on the 100-point scale, equaling an average 11.7-point decline for the cannabidiol group and an 11.5-point decline for the placebo group. Summarized using an alternative indicator of pain improvement, at the end of the trial only 22% of the cannabidiol-group subjects and 21% of the placebo-group subjects experienced at least a 30-point reduction on the pain scale, and this 1% difference between the two groups was not statistically significant.

The researchers also found no statistically significant differences between the cannabidiol and placebo groups on measures of sleep quality, depression, anxiety or pain catastrophizing scores at 12 weeks.

Finally, the researchers noted that although they found no adverse effects associated with cannabidiol use, their trial was not large enough to detect uncommon adverse events. Prior clinical trials, especially epilepsy trials where other seizure medications were combined with cannabidiol at doses exceeding 300 mg per day, found that cannabidiol use was associated with decreased appetite, diarrhea, sedation and sleepiness.

The researchers concluded that their trial represented the first large, randomized placebo-controlled trial to assess the effect of cannabidiol on chronic pain of moderate or greater intensity. They further concluded that their trial found no evidence that cannabidiol was effective for treating pain due to osteoarthritis or psoriatic arthritis.

What You Can Do

Do not use cannabidiol to treat the pain associated with osteoarthritis, psoriatic arthritis or any other form of chronic pain. Instead, first use nonpharmacologic interventions like weight loss, exercise and joint braces. If those approaches do not provide sufficient relief, then try using a topical or oral NSAID to alleviate your pain. If the addition of NSAIDs is unsuccessful at offering pain relief, consult with your physician about additional pain-management approaches. In the case of psoriatic arthritis, you may need to consult with your doctor about the use of DMARDs (for example, methotrexate [OTREXUP, RASUVO, REDITREX, TREXALL, XATMEP], adalimumab [ABRILADA, AMJEVITA, CYLTEZO, HADLIMA, HULIO, HUMIRA, HYRIMOZ, YUSIMRY], and infliximab [AVSOLA, INFLECTRA, IXIFI, REMICADE, RENFLEXIS]) to alleviate your pain and other symptoms specific to that autoimmune disease.
 

References

[1] National Center for Complementary and Integrative Medicine. National Institutes of Health. Cannabis (marijuana) and cannabinoids: what you need to know. November 2019. https://www.nccih.nih.gov/health/cannabis-marijuana-and-cannabinoids-what-you-need-to-know. Accessed January 7, 2022.

[2] National Institute on Drug Abuse. Marijuana Research Report. July 2020. https://www.drugabuse.gov/download/1380/marijuana-research-report.pdf. Accessed January 7, 2022.

[3] Harvard Health Publishing. Cannabidiol (CBD) — what we know and what we don’t. August 27, 2019. https://www.health.harvard.edu/blog/cannabidiol-cbd-what-we-know-and-what-we-dont-2018082414476. Accessed January 7, 2022.

[4] Greenwich Biosciences, Inc. Label: cannabidiol (EPIDIOLEX). September 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/210365s012s013lbl.pdf. Accessed January 7, 2022.

[5] Fisher E, Moore RA, Fogarty AE, et al. Cannabinoids, cannabis, and cannabis-based medicine for pain management: a systematic review of randomised controlled trials. Pain. 2021;162(7, Suppl 1):S45-S66.

[6] Rice ASC, Belton J, Arendt Nielsen L. Presenting the outputs of the IASP Presidential Task Force on Cannabis and Cannabinoid Analgesia. Pain. 2021;162(7, Suppl 1):S3-S4.

[7] Centers for Disease Control and Prevention. Fast facts about arthritis. October 12, 2021. https://www.cdc.gov/arthritis/basics/arthritis-fast-facts.html. Accessed January 7, 2022.

[8] National Institute of Arthritis and Musculoskeletal and Skin Disease. Arthritis basics. April 2017. https://www.niams.nih.gov/health-topics/arthritis. Accessed January 7, 2022.

[9] Center for Disease Control and Prevention. Fast facts about arthritis. October 12, 2021. https://www.cdc.gov/arthritis/basics/arthritis-fast-facts.html. Accessed January 7, 2022.

[10] Center for Disease control and Prevention. Osteoarthritis (OA). July 27, 2020. https://www.cdc.gov/arthritis/basics/osteoarthritis.htm. Accessed January 7, 2022.

[11] Hunter TM, Boytsov NN, Zhang X, et al. Prevalence of rheumatoid arthritis in the United States adult population in healthcare claims databases, 2004-2014. Rheumatol Int. 2017;37(9):1551-1557.

[12] Gladman DD, Ritchlin C. Clinical manifestations and diagnosis of psoriatic arthritis. UpToDate. May 1, 2020.

[13] Gladman DD, Ritchlin C. Treatment of psoriatic arthritis. UpToDate. November 20, 2020.

[14] Deveza LA. Overview of management of osteoarthritis. UpToDate. March 24, 2021.

[15] Vela J, Dreyer L, Petersen KK, et al. Cannabidiol treatment in hand osteoarthritis and psoriatic arthritis: a randomized, double-blind placebo-controlled trial. Pain. 2021 Aug 27. doi: 10.1097/j.pain.0000000000002466. Epub ahead of print.

[16] Petrini L, Arendt-Nielsen L. Understanding pain catastrophizing: putting pieces together. Front Psychol. 2020;11:603420.